An experimental pill has achieved complete remission of the cancer in 18 patients sentenced to near death by a very aggressive tumor that has not responded to other treatments. The disease, acute myeloid leukemia, is the most common blood cancer in adults, with approximately 120,000 cases per year, and the three-year survival rate barely reaches 25%. The pill, called revumenib, has achieved complete disappearance of the signs of cancer in nearly one in three participants in an anticipated clinical trial in the United States. The results are preliminary and do not imply a definitive cure, but those in charge of the experiment are optimistic. “We believe this drug is remarkably effective and we hope it will be available to all patients who need it,” says Dr. Ghayas Issa of the University of Texas MD Anderson Cancer Center.
Acute myeloid leukemia hits the blood cell factory – the marrow of the bones – and causes an uncontrolled production of defective cells. That’s what happened to 23-year-old Lithuanian architect Algimante Daugelaite. After her sister’s two bone marrow transplants and all treatments had failed, her doctors already considered palliative care to simply alleviate her suffering. “I was devastated, it was like witnessing a terrible movie. I felt like death was imminent and I was only 21 years old,” he recalls. Exactly two years ago he started taking Revumenib pills, was able to complete his studies and now works quite normally in an architect’s office in Copenhagen.
The drug does not work in all cases. Researchers have focused on two genetic subtypes in which a protein called menin facilitates leukemia progression. Revumenib binds to this protein and inhibits it thanks to its complicated chemical formula: 32 carbon atoms, 47 hydrogen, one fluorine, six nitrogen, four oxygen and one sulphur. This formula, C32H47FN6O4S, has saved 18 lives so far. The promising results will be published this Wednesday in the journal Nature, a benchmark for the best science in the world.
I felt like death was imminent and I was only 21 years old.”
Algimante Daugelaite, architect
Hematologist Pau Montesinos, coordinator of the Spanish Acute Myeloid Leukemia Group, believes the new data are “quite encouraging” but stresses his caution and is waiting for revumenib to be tested on hundreds of people and its safety and effectiveness confirmed. Montesinos’ own team, the Leukemia Unit of the La Fe Hospital in Valencia, will take part in the forthcoming international trials of the pill developed by the American pharmaceutical company Syndax Pharmaceuticals.
Montesinos emphasizes that the drug alone is not a panacea. “These targeted therapies alone can reverse the leukemia in the vast majority of cases, but they can hardly cure it,” says the haematologist. “The strategy will be to combine these new drugs with classic chemotherapeutic agents or with other approaches,” he says. Montesinos recalls the case of another pill, quizartinib, an experimental treatment by Japanese pharmaceutical company Daiichi Sankyo, that inhibits another protein implicated in acute myeloid leukemia. Adding quizartinib to chemotherapy increases cure rates from nearly 40% to nearly 50%, according to preliminary results from a study of 500 patients with a different genetic subtype. “For us, an increase in the survival rate by 10 percentage points is a lot,” says the Spanish doctor happily.
The mechanism of action of revumenib – inhibition of the menin protein – is new. Half a dozen drug companies are developing drugs that use the same tactics, so revumenib’s success would be good news for the rest of the meningeal inhibitor community. Oncologist Ghayas Issa estimates that these new pills could benefit nearly 400,000 people with acute leukemia resistant to other treatments, both myeloid and the most common in children, called lymphocytic.
These targeted therapies alone can reverse leukemia but are unlikely to cure it.”
Pau Montesinos, haematologist
Issa and his colleagues recognize that the economic factor will be crucial when the pill is finally approved. According to a report by Democratic Congresswoman Katie Porter, the price of the latest oral cancer drugs in the United States typically exceeds €200,000 per patient per year.
Revumenib has another weakness, admits another scientist who led the studies, hematologist Eytan Stein of Memorial Sloan Kettering Cancer Center in New York. “The main Achilles’ heel seems to be the development of mutations in the binding site of this drug that create resistance,” explains the researcher. Revumenib had some kind of positive effect in half of the 60 participants in the clinical trial, but in some patients the menin protein changed slightly and resistance to the treatment emerged, just like bacteria that mutate and tolerate antibiotics.
“This shows that we are on the right track and that the goal this drug is aimed at is on target [la proteína menina] it is crucial for the development of leukemia in these genetic subtypes,” says Stein. To avoid these resistance mutations observed in some patients, the authors propose combining drugs with different mechanisms of action. According to Ghayas Issa and his colleague Eytan Stein, menin inhibitors “will definitely be part of the treatment of these leukemias”. Architect Algimante Daugelaite is delighted to have participated in the process and that science has given her “another opportunity to study, work, travel, see the world and above all live”.
you can follow THEME on Facebook, Twitter and Instagram, or sign up here to receive our weekly newsletter.